Pharmacogenetics of Doxazosin for Cocaine Dependence: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pharmacogenetics of Doxazosin for Cocaine Dependence (NCT01145183), a randomized phase 2 study. The primary outcome is Percentage of Cocaine Positive Urine Toxicology.

2. Clinical Question

The trial asks whether doxazosin is associated with a change in cocaine-use behavior, assessed through cocaine-positive urine toxicology, compared with matched placebo. Its stated pharmacogenetic aim is to evaluate whether prospective screening for catecholamine-related polymorphisms predicts doxazosin treatment efficacy. The brief summary identifies alpha 1 norepinephrine receptor and transporter targets, COMT, and DBH as the main targets of interest.

The question is clinically framed around urine toxicology rather than a single self-reported measure of cocaine use. The stated endpoint is recorded in two-week blocks throughout the study, so the intended outcome captures repeated observations over time. The registry record does not specify how the genetic screening categories were defined, how participants were assigned to those categories for analysis, or whether a treatment-by-genotype comparison was performed. It also does not report an estimate of the treatment contrast or its uncertainty. The record therefore describes the research question and outcome, but does not establish whether the observed data support a particular answer.

3. Trial Design

The registry classifies this as a Phase 2, randomized, quadruple-masked, parallel-group trial. The listed interventions are doxazosin and placebo. The trial status is completed, and the registry reports enrollment of 96. Baylor College of Medicine is listed as sponsor. The record gives a start date of 2010-03 and a primary completion date of 2015-09.

In a randomized design, assignment to trial groups is intended to support a fair comparison by reducing systematic differences between groups at baseline. Randomization does not itself guarantee that every measured or unmeasured factor is balanced, and the registry record does not give the allocation sequence or the method used to generate it. “Quadruple” masking is the registry’s classification; the record does not identify which participant, investigator, or other roles were masked, or describe how masking was maintained.

The parallel model indicates that the listed arms are separate groups rather than a crossover sequence. The doxazosin arm description identifies a long-acting and selective alpha 1-norepinephrine blocker and says it inhibits norepinephrine binding to alpha receptors in the autonomic nervous system. The placebo arm description states matched placebo daily dosing. Doses, titration, treatment duration, adherence, and concomitant care are not reported in the registry record.

The primary outcome is the percentage of cocaine-positive urine toxicology results, with measurements described in two-week blocks throughout the study. Adverse events are listed as a secondary outcome. The registry identifies two outcome measures, but does not provide a detailed schedule for safety monitoring or additional outcome definitions. The record does not report a protocol-based sample-size justification, a detailed statistical analysis plan, or the procedures used to handle repeated observations. These omissions limit how fully the design and analysis can be reconstructed from the registry record alone.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: Thus, 96 individuals entered into the study and were randomly assigned into the doxazosin or the placebo groups. Following randomization, 7 participants were lost to follow up and 13 opted out of the pharmacogenetic testing. In total, 76 CUD patients participated in this trial.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Cocaine Positive Urine Toxicology, measured over 2 weeks blocks throughout study.

The primary endpoint is titled “Percentage of Cocaine Positive Urine Toxicology.” Its unit is a percentage of positive urines, and the registry describes the measure as cocaine-positive urines recorded in two-week blocks throughout the study. In practical terms, a percentage expresses positive test results relative to the urine results included in the calculation. The registry record does not specify the denominator used for each block, how missing or unusable specimens were treated, or whether the reported outcome was calculated separately for each participant before group comparisons.

Urine toxicology is used in this trial as an objective indicator of cocaine exposure during the period covered by specimen collection. Repeated measurements can describe whether positive tests occur across successive study periods rather than relying on a single observation. As a general statistical point, repeated measurements from one participant may be related to one another; an analysis that treats them as independent can understate uncertainty if that relationship is ignored. The registry record does not report the model used to account for repeated measures.

The endpoint’s title indicates a percentage, but the registry classifies its result type as a number and does not report an outcome value, group estimate, treatment contrast, or confidence interval. The record therefore defines what the outcome is intended to measure, but does not provide enough information to interpret the magnitude or precision of an observed treatment effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies a randomized, quadruple-masked, parallel Phase 2 trial, but it does not report the detailed statistical methods used for the primary outcome. The following concepts are general statistical explanations, not claims about analyses performed in this trial.

What does randomization contribute?

Random assignment is intended to make treatment groups comparable, on average, with respect to factors that could influence the outcome. This helps support a causal interpretation of a between-group comparison when the trial is conducted and analyzed appropriately. Randomization does not ensure exact balance in every characteristic, particularly in a finite study, and it cannot correct problems arising after assignment, such as differential missing outcome data. The registry identifies randomization but does not describe the sequence-generation method, concealment procedures, or baseline characteristics.

How should repeated urine measurements be handled?

The endpoint is described as a percentage of positive urines measured in two-week blocks throughout the study. This implies repeated outcome information over time, but the registry record does not specify the analytic unit or model. In general, repeated observations from the same participant may be correlated: a participant’s test result in one period can be related to results in other periods. A suitable analysis can account for that dependence, whereas treating all observations as independent may make standard errors and confidence intervals too small. The exact method depends on how the data are recorded, the estimand of interest, and assumptions about the outcome and missingness; none of those choices is reported in the registry record.

Why does the outcome scale matter?

A percentage of positive urines is a proportion-based outcome. General statistical methods for proportions may account for the number of tests contributing to each percentage and for within-participant dependence. If a model assumes more variability than its basic form allows, over-dispersion can make conventional uncertainty estimates too optimistic. Over-dispersion is a general issue to consider for count or proportion data; the registry does not say whether it was assessed or how it was handled in this trial. The result type is listed as a number, and no distributional model is identified.

What would an interpretable comparison contain?

For a group comparison, an estimate should identify the outcome contrast and the population and time period to which it applies. A confidence interval would describe uncertainty around that estimate under the selected model. A test result may accompany the estimate, but a test result alone would not show the size or precision of the difference. The registry record does not report a primary-outcome estimate, confidence interval, or test result, and it does not define a single comparison across the multiple categories or time points.

What does the planning note mean?

The registry’s planning note describes an illustration based on an observed effect, a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. It also says that the effect to detect is a stated fraction of the observed effect. Such calculations can illustrate how planning requirements change under specified assumptions, but they do not describe the actual trial’s design rationale unless the protocol says they were used for that purpose. The protocol-based sample-size justification is not reported in the registry record. No numerical planning values are reported, and these illustrations are not observed power.

What can be concluded from the absence of a reported analysis?

The registry lists zero analyses and does not reduce the primary outcome’s multiple time points or categories to one comparison. This is a limitation of the information recorded, not proof that no analysis was ever conducted outside the registry. Statistical conclusions should be based on documented estimates and methods; without them, neither the direction of an effect nor its uncertainty can be evaluated from this record. The model, covariate adjustments, treatment of repeated measures, and analysis population are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome is recorded across two-week blocks throughout the study, and the registry explicitly indicates that it was not reduced to one comparison because it has several categories or time points. The record does not state which time point or summary measure was designated as the principal efficacy contrast, or how multiple comparisons were to be handled. It also does not report whether interim analyses were planned or performed. These details are not reported in the registry record.

Multiplicity matters when several related hypotheses or time points are tested. As a general statistical principle, conducting many tests without an appropriate strategy can increase the chance of at least one apparently unusual result under a null model. Possible approaches depend on the research question and analysis plan; the registry record does not identify an approach for this trial. Because there is no reported primary comparison, the record does not support a multiplicity-adjusted or unadjusted efficacy conclusion.

The registry does not describe the amount or pattern of missing urine toxicology data, reasons for missingness, or the method used to handle missing observations. It does not report whether analyses followed an intention-to-treat approach, a per-protocol approach, or another defined population. Enrollment should not be assumed to equal the number contributing to the primary analysis. The handling of missing outcome data and the analysis populations are not reported in the registry record.

These omissions matter because missingness and the choice of analysis population can affect both the estimate and its uncertainty. In general, an analysis should make clear which randomized participants and which observed measurements contribute, and should explain assumptions about unavailable outcomes. Without those descriptions or reported estimates, readers cannot assess the robustness of an efficacy finding from the registry record.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry lists adverse events as a secondary outcome. For the doxazosin group, it records 47 at risk, 0 serious adverse events, 47 at risk for other adverse events, 0 other adverse events, and 0 deaths. For the placebo group, it records 29 at risk, 0 serious adverse events, 29 at risk for other adverse events, 0 other adverse events, and 0 deaths. No top serious adverse-event terms are listed.

These entries describe what the registry reports for the recorded safety categories. A value of 0 means that no event was entered for that category in this record; it does not, by itself, establish that no symptoms or medical events of any kind occurred. The record does not provide event definitions, the observation period for safety, severity categories beyond the serious-event designation, or information about how events were collected and adjudicated.

At-risk counts are safety denominators and should not automatically be treated as efficacy-analysis counts. The record does not explain differences between these safety counts and the overall enrollment, or whether all participants had the same duration of safety follow-up. Without event definitions and follow-up details, the safety entries should be read narrowly as registry-reported counts, not as a complete account of tolerability or comparative risk.

12. What the Result Does, and Does Not, Mean

The record establishes that the study was completed and that its stated primary outcome concerned cocaine-positive urine toxicology, recorded in two-week blocks throughout the study. It also establishes that the trial compared doxazosin with matched placebo in a randomized, quadruple-masked, parallel design. These are descriptions of the study’s design and intended measurement, not evidence of a treatment effect.

The registry does not report a reduced primary-outcome comparison, an estimate of the difference between groups, a confidence interval, or a statistical test result. Accordingly, the record cannot show whether the groups differed, in which direction they may have differed, or how precisely any difference was estimated. The absence of a reported comparison must not be interpreted as a finding of no difference. It also cannot be interpreted as evidence that doxazosin changed cocaine-use behavior.

The trial’s pharmacogenetic objective raises a separate question: whether screening for the specified catecholamine-related polymorphisms predicts treatment efficacy. The registry record describes that objective but supplies no genotype-specific results or interaction analysis. It therefore does not establish that screening predicted a response, nor does it establish that it did not.

The safety entries list zero serious adverse events, zero other adverse events, and zero deaths in both groups as recorded in the registry. These entries are limited to the categories and counts reported; they do not replace a full safety report or clarify the duration and completeness of event collection.

General statistical interpretation depends on more than whether a result is labeled significant. Readers need to know the estimated effect, its uncertainty, the outcome definition, the analysis population, and the assumptions used to analyze repeated measurements and missing data. The registry record does not report these details for the primary outcome. Thus, it supports a description of the research question and trial framework, but not a conclusion about efficacy, precision, or pharmacogenetic prediction.

13. Why This Trial Matters Statistically

This trial is statistically notable because its primary outcome is collected repeatedly and expressed as the percentage of positive urine toxicology results. Such an outcome can be understood as a series of measurements rather than a single endpoint at one time. The choice of summary and the handling of correlation among repeated observations can materially shape the estimate and its uncertainty. The registry record does not report the model used, making the analysis strategy impossible to assess from the record.

The pharmacogenetic objective also involves a different inferential question from a simple comparison of treatment groups. To assess whether a genetic marker predicts treatment efficacy, an analysis generally needs to examine whether the treatment contrast varies across marker-defined groups. A pattern within one group alone does not establish that a marker predicts differential treatment response. This is a general statistical distinction; the registry record does not report an interaction analysis or genotype-specific results.

The record also illustrates why a completed-trial status is not equivalent to a reported efficacy result. The trial has a defined design, interventions, and primary outcome, yet no single primary comparison or analysis result is recorded. Without the estimate and its precision, readers cannot judge the magnitude, direction, or uncertainty of the intended comparison. The record’s planning note describes assumptions for an illustration, but does not supply numerical planning results or a protocol-based sample-size justification.

Finally, the safety counts and efficacy question answer different questions. Safety entries enumerate recorded adverse-event categories, while the primary endpoint concerns urine toxicology. Neither set of information can stand in for the other. The statistical importance of the record is therefore as much about what remains undocumented—analysis methods, missing-data handling, outcome estimates, and genetic comparisons—as about the trial framework that is stated.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main trial-specific limitation in the registry record is the absence of a reported primary-outcome comparison. The endpoint is described as having several categories or time points and is not reduced to one comparison. The record lists zero analyses and provides no group estimates, contrast, confidence interval, or test result. This prevents assessment of the observed efficacy pattern and its precision.

The outcome definition is incomplete for reconstructing an analysis. Although the registry identifies the percentage of cocaine-positive urine toxicology results and a two-week-block timeframe, it does not specify the denominator for each percentage, the handling of missing or unusable samples, or the way repeated measurements were combined or modeled. It does not report the analysis population or whether any covariates were included.

The registry describes a prospective pharmacogenetic objective but does not report the specific screening categories, genotype frequencies, treatment-by-genotype analysis, or results. It therefore cannot establish how the genetic question was tested. Detailed eligibility criteria, dosing, treatment duration, adherence procedures, and masking procedures are also not reported in the registry record.

The record does not provide a protocol-based sample-size justification, a statistical analysis plan, an interim-analysis description, or a multiplicity strategy. It gives a planning note with assumptions but no numerical planning outputs. Missing-data amounts and methods are not reported. These gaps limit reproducibility and make it difficult to judge whether the reported registry outcome framework matches the analyses that may have been conducted elsewhere.

The safety record is also limited: event definitions, collection procedures, follow-up duration, and details about the completeness of reporting are not stated. The listed zero counts should therefore be interpreted only as registry entries for the reported categories, not as a comprehensive account of all events during the trial.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pharmacogenetics of Doxazosin for Cocaine Dependence — NCT01145183.
• Registry record last updated 2019-07-22; status last verified 2019-07.
• Results first posted 2019-07-22.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT01145183, “Pharmacogenetics of Doxazosin for Cocaine Dependence,” is listed as a completed Phase 2 randomized, quadruple-masked, parallel trial sponsored by Baylor College of Medicine. The registry reports enrollment of 96, a start date of 2010-03, and primary completion on 2015-09. The listed interventions are doxazosin and matched placebo.

The primary outcome is the percentage of cocaine-positive urine toxicology results, measured in two-week blocks throughout the study. The stated objective includes evaluating whether prospective screening for catecholamine-related polymorphisms predicts doxazosin efficacy. Adverse events are listed as a secondary outcome.

The registry record does not report a single primary-outcome comparison, an efficacy estimate, a confidence interval, or analysis methods. It lists zero analyses. Safety entries record zero serious adverse events, zero other adverse events, and zero deaths in both groups. The record does not report the protocol-based sample-size justification, missing-data methods, analysis populations, or genetic-analysis results.